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1.	Kahn, Robin, et al. (författare) Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms 2022 Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:2, s. 354-62 Tidskriftsartikel (refereegranskat)abstract Aim: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Methods: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8weeks after diagnosis are presented, and follow-up protocols are suggested. Results: We identified 152 cases, and 133 (87%) participated. When followed up 2weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. Conclusion: More than a third (36%) of the patients had persistent symptoms 8weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.
2.	Rosengren, Annika, 1951, et al. (författare) Severe COVID-19 in people 55 and older during the first year of the pandemic in Sweden 2022 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796 .- 0955-7873. ; 292:4, s. 641-653 Tidskriftsartikel (refereegranskat)abstract Background Exposure to many contacts is the main risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while risk of serious disease and death is chiefly determined by old age and comorbidities. Relative and population-attributable fractions (PAFs) of multiple medical and social exposures for COVID-19 outcomes have not been evaluated among older adults. Objectives We describe the effect of multiple exposures on the odds of testing positive for the virus and of severe disease (hospital care or death) and PAFs in Swedish citizens aged 55 years and above. Methods We used national registers to follow all citizens aged 55 years and above with respect to (1) testing positive, (2) hospitalization, and (3) death between 31 January 2020 and 1 February 2021. Results Of 3,410,241 persons, 156,017 (4.6%, mean age 68.3 years) tested positive for SARS-CoV-2, while 35,999 (1.1%, mean age 76.7 years) were hospitalized or died (12,384 deaths, 0.4%, mean age 84.0 years). Among the total cohort, the proportion living without home care or long-term care was 98.8% among persons aged 55-64 and 22.1% of those aged 95 and above. After multiple adjustment, home care and long-term care were associated with odds ratios of 7.9 (95% confidence interval [CI] 6.8-9.1) and 22.5 (95% CI 19.6-25.7) for mortality, with PAFs of 21.9% (95% CI 20.9-22.9) and 33.3% (95% CI 32.4-34.3), respectively. Conclusion Among Swedish residents aged 55 years and above, those with home care or long-term care had markedly increased risk for COVID-19 death during the first year of the pandemic, with over 50% of deaths attributable to these factors.
3.	Helldén, Anders, et al. (författare) Aciclovir- a nearly atoxic antiviral drug with severe neurotoxic side effects. A retrospective review of 280 cases and the importance of analysing the aciclovir metabolite CMMG. 2008 Ingår i: 2nd World Conference on Magic Bullets (Ehrlich II) Nürnberg, Germany 2008. Konferensbidrag (refereegranskat)abstract Aciclovir- a nearly atoxic antiviral drug with severe neurotoxic side effects. A retrospective review of 280 cases and the importance of analysing the aciclovir metabolite CMMG.
4.	Andersson, Maria Eva, et al. (författare) Rapid Clearance and Frequent Reinfection With Enteric Pathogens Among Children With Acute Diarrhea in Zanzibar. 2017 Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 65:8, s. 1371-1377 Tidskriftsartikel (refereegranskat)abstract Background: Acute infectious gastroenteritis is an important cause of illness and death among children in low-income countries. In addition to rotavirus vaccination, actions to improve nutrition status, sanitation, and water quality are important to reduce enteric infections, which are frequent also among asymptomatic children. The aim of this study was to investigate if the high prevalence of these infections reflects that they often are not cleared properly by the immune response or rather is due to frequent pathogen exposure.Methods: Rectal swabs were collected at time of acute diarrhea and 14 days later from 127 children, aged 2-59 months and living in rural Zanzibar, and were analyzed by real-time polymerase chain reaction targeting multiple pathogens.Results: At baseline, detection rates >20% were found for each of enterotoxigenic Escherichia coli, Shigella, Campylobacter, Cryptosporidium, norovirus GII, and adenovirus. At follow-up, a large proportion of the infections had become cleared (34-100%), or the pathogen load reduced, and this was observed also for agents that were presumably unrelated to diarrhea. Still, the detection frequencies at follow-up were for most agents as high as at baseline, because new infections had been acquired. Neither clearance nor reinfection was associated with moderate malnutrition, which was present in 21% of the children.Conclusions: Children residing in poor socioeconomic conditions, as in Zanzibar, are heavily exposed to enteric pathogens, but capable of rapidly clearing causative and coinfecting pathogens.
5.	Rosengren, Annika, 1951, et al. (författare) COVID-19 in people aged 18–64 in Sweden in the first year of the pandemic: Key factors for severe disease and death 2022 Ingår i: Global Epidemiology. - : Elsevier BV. - 2590-1133. ; 4 Tidskriftsartikel (refereegranskat)abstract Background: Studies on risk factors for severe COVID-19 in people of working age have generally not included non-working persons or established population attributable fractions (PAFs) for occupational and other factors. Objectives: We describe the effect of job-related, sociodemographic, and other exposures on the incidence, relative risks and PAFs of severe COVID-19 in individuals aged 18–64. Methods: We conducted a registry-based study in Swedish citizens aged 18–64 from 1 January 2020 to 1 February 2021 with respect to COVID-19-related hospitalizations and death. Results: Of 6,205,459 persons, 272,043 (7.5%) were registered as infected, 3399 (0.05%) needed intensive care, and 620 (0.01%) died, with an estimated case fatality rate of 0.06% over the last 4-month period when testing was adequate. Non-Nordic origin was associated with a RR for need of intensive care of 3·13, 95%CI 2·91–3·36, and a PAF of 32·2% after adjustment for age, sex, work, region and comorbidities. In a second model with occupation as main exposure, and adjusted for age, sex, region, comorbidities and origin, essential workers had an RR of 1·51, 95%CI, 1·35–1·6, blue-collar workers 1·18, 95%CI 1·06–1·31, school staff 1·21, 95%CI 1·01–1·46, and health and social care workers 1·89, 95%CI 1·67–2·135) compared with people able to work from home, with altogether about 13% of the PAF associated with these occupations. Essential workers and blue-collar workers, but no other job categories had higher risk of death, adjusted RRs of 1·79, 95%CI 1·34–2·38 and 1·37, 95%CI 1·04–1·81, with adjusted PAFs of altogether 9%. Conclusion: Among people of working age in Sweden, overall mortality and case fatality were low. Occupations that require physical presence at work were associated with elevated risk of needing intensive care for COVID-19, with 14% cases attributable to this factor, and 9% of deaths.
6.	Aydogdu, Özgu, 1978, et al. (författare) Urinary tract infection: Europe. 2011 Ingår i: Guide to Pediatric Urology and Surgery in Clinical Practice. - 9781849963664 ; , s. 21-34 Bokkapitel (övrigt vetenskapligt/konstnärligt)
7.	Einarsdottir, Sigrun, et al. (författare) Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity. 2022 Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:9, s. 2723-2730 Tidskriftsartikel (refereegranskat)abstract Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlapS1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/mL) of anti-RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P = .007, Fisher's exact test). We conclude that although allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses.
8.	Khassebaf, Jasmine, et al. (författare) Antibiotic susceptibility of Propionibacterium acnes isolated from orthopaedic implant-associated infections 2015 Ingår i: Anaerobe. - : Elsevier. - 1075-9964 .- 1095-8274. ; 32, s. 57-62 Tidskriftsartikel (refereegranskat)abstract Introduction: Prosthetic joint infections (PJIs) caused by Propionibacterium acnes account for a larger proportion of the total number of PJIs than previously assumed and thus knowledge of the antimicrobial susceptibility patterns of P. acnes is of great value in everyday clinical practice.Materials and methods: Using Etest, the present study investigated the susceptibility of 55 clinical isolates of P. acnes, obtained from orthopaedic implant-associated infections of the knee joint (n = 5), hip joint (n = 17), and shoulder joint (n = 33), to eight antimicrobial agents: benzylpenicillin, clindamycin, metronidazole, fusidic acid, doxycycline, moxifloxacin, linezolid and rifampicin. Synergy testing was also conducted, in which rifampicin was combined with each of the remaining seven antibiotics.Results: All isolates (n = 55) were susceptible to most of the antibiotics tested, with the exception of 100% resistance to metronidazole, five (9.1%) isolates displaying decreased susceptibility to clindamycin, and one (1.8%) to moxifloxacin. None of the antimicrobial agents investigated were synergistic with each other when combined and nine isolates were antagonistic for various antimicrobial combinations. The majority of the antimicrobial combinations had an indifferent effect on the isolates of P. acnes. However, the combination of rifampicin and benzylpenicillin showed an additive effect on nearly half of the isolates.Conclusion: Almost all P. acnes, isolated from orthopaedic implant-associated infections, predominantly PJIs, were susceptible to the antibiotics tested, with the exception of complete resistance to metronidazole. Synergy test could not demonstrate any synergistic effect but additive effects were found when combining various antibiotics. Antagonistic effects were rare.
9.	Westman, Gabriel, 1977-, et al. (författare) Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis. 2021 Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 27:8, s. 1131-1136 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: The aim was to investigate the correlation between biomarkers of brain injury and long-term neurocognitive outcome, and the interplay with intrathecal inflammation and neuronal autoimmunity, in patients with herpes simplex encephalitis (HSE).METHODS: A total of 53 adult/adolescent HSE patients were included from a prospective cohort in a randomized placebo-controlled trial investigating the effect of a 3-month follow-up treatment with valaciclovir. Study subjects underwent repeated serum/cerebrospinal fluid (CSF) sampling and brain magnetic resonance imaging in the first 3 months along with cognitive assessment using the Mattis Dementia Rating Scale (MDRS) at 24 months. CSF samples were analysed for biomarkers of brain injury, inflammation and synaptic autoimmunity. The predefined primary analysis was the correlation between peak CSF neurofilament protein (NFL), a biomarker of neuronal damage, and MDRS at 24 months.RESULTS: Impaired cognitive performance significantly correlated with NFL levels (rho = -0.36, p = 0.020). Development of IgG anti-N-methyl-D-aspartate receptor (NDMAR) antibodies was associated with a broad and prolonged proinflammatory CSF response. In a linear regression model, lower MDRS at 24 months was associated with previous development of IgG anti-N-methyl-D-aspartate receptor (NMDAR) (beta = -0.6249, p = 0.024) and age (z-score beta = -0.2784, p = 0.024), but not CSF NFL, which however significantly correlated with subsequent NMDAR autoimmunization (p = 0.006).DISCUSSION: Our findings show that NFL levels are predictive of long-term neurocognitive outcome in HSE, and suggest a causative chain of events where brain tissue damage increases the risk of NMDAR autoimmunisation and subsequent prolongation of CSF inflammation. The data provides guidance for a future intervention study of immunosuppressive therapy administered in the recovery phase of HSE.
10.	Buchwald, Fredrik, et al. (författare) Fatal course of cerebral vasculitis induced by neuroborreliosis. 2010 Ingår i: Neurology India. - : Medknow. - 0028-3886. ; 58:1, s. 139-141 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
11.	Malmberg, Stefan, 1979, et al. (författare) Acute sore throat and Fusobacterium necrophorum in primary healthcare: a systematic review and meta-analysis. 2021 Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:6 Forskningsöversikt (refereegranskat)abstract The main objective of this review was to describe and quantify the association between Fusobacterium necrophorum (FN) and acute sore throat in primary healthcare (PHC).In this systematic review and meta-analysis, we searched Scopus and PubMed for case-control studies reporting the prevalence of FN in patients attending primary care for an uncomplicated acute sore throat as well as in healthy controls. Only studies published in English were considered. Publications were not included if they were case studies, or if they included patients prescribed antibiotics before the throat swab, patients with a concurrent malignant disease, on immunosuppression, having an HIV infection, or patients having another acute infection in addition to a sore throat. Inclusion criteria and methods were specified in advance and published in PROSPERO. The primary outcome was positive etiologic predictive value (P-EPV), quantifying the probability for an association between acute sore throat and findings of FN in the pharynx. For comparison, our secondary outcome was the corresponding P-EPV for group A Streptococcus (GAS).PubMed and Scopus yielded 258 and 232 studies, respectively. Removing duplicates and screening the abstracts resulted in 53 studies subsequently read in full text. For the four studies of medium to high quality included in the meta-analysis, the cumulative P-EPV regarding FN was 64% (95% CI 33% to 83%). GAS, based on data from the same publications and patients, yielded a positive EPV of 93% (95% CI 83% to 99%).The results indicate that FN may play a role in PHC patients with an acute sore throat, but the association is much weaker compared with GAS.
12.	Karlsson, Caroline, et al. (författare) 5-Hydroxytryptamine contracts human uterine artery smooth muscle predominantly via 5-HT2 receptors 1997 Ingår i: Human Reproduction. - 0268-1161. ; 12:2, s. 361-367 Tidskriftsartikel (refereegranskat)abstract Serotonergic receptors were classified in the isolated human uterine artery with intact endothelium, using agonists and antagonists for 5-hydroxytryptamine (5-HT) receptors. The efficacy for different agonists rated: alpha-methyl-5-HT (5-HT2) = 5-HT (non-selective) = 2-methyl-5-HT (5-HT3) >> sumatriptan (5-HT1), and the potency as: sumatriptan = 5-HT > 5-HT > alpha-methyl-5-HT > 2-methyl-5-HT. The contractile effects of 5-HT and alpha-methyl-5-HT were antagonized by the 5-HT2 receptor antagonist ketanserin and the non-selective antagonist methiothepin. The efficacy of sumatriptan was comparatively low. No interaction was encountered between 2-methyl-5-HT and MDL72222, suggesting an absence of 5-HT3 receptors. The results indicate that the contractile serotonergic receptor population in the human uterine artery mainly comprises 5-HT2 receptors, although a minor contribution of contractile 5-HT1 receptors cannot be excluded.
13.	Karlsson, Caroline, et al. (författare) Characterization of 5-hydroxytryptamine receptors mediating circular smooth muscle contraction in the human umbilical artery 1999 Ingår i: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 1423-002X .- 0378-7346. ; 47:2, s. 102-107 Tidskriftsartikel (refereegranskat)abstract The study was performed to characterize pharmacologically the contractile 5-hydroxytryptamine (5-HT) receptors in the circular smooth muscle of the isolated human umbilical artery. Effects of agonists and antagonists for different 5-HT receptor subtypes were studied in intact endothelium vessel segments. All agonists induced concentration-dependent circular smooth muscle contractions. The potency was in declining order 5-HT > alpha-methyl-5-HT > sumatriptan >/= 2-methyl-5-HT. The effects of 5-HT and alpha-methyl-5-HT were antagonized by ketanserin, as well as methiothepin. The contractile effect of sumatriptan was antagonized by methiothepin but not by ketanserin. The 5-HT3 receptor antagonist, MDL 72222, did not affect the contraction by any of the agonists, including 2-methyl-5-HT. It is concluded that the 5-HT-induced contraction in the circular smooth muscle of the human umbilical artery seems to be mediated by a mixed population of 5-HT1-like receptors and 5-HT2 receptors.
14.	Svensson, Katrin, et al. (författare) Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells. 2011 Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 108:32, s. 13147-13152 Tidskriftsartikel (refereegranskat)abstract Highly malignant tumors, such as glioblastomas, are characterized by hypoxia, endothelial cell (EC) hyperplasia, and hypercoagulation. However, how these phenomena of the tumor microenvironment may be linked at the molecular level during tumor development remains ill-defined. Here, we provide evidence that hypoxia up-regulates protease-activated receptor 2 (PAR-2), i.e., a G-protein-coupled receptor of coagulation-dependent signaling, in ECs. Hypoxic induction of PAR-2 was found to elicit an angiogenic EC phenotype and to specifically up-regulate heparin-binding EGF-like growth factor (HB-EGF). Inhibition of HB-EGF by antibody neutralization or heparin treatment efficiently counteracted PAR-2-mediated activation of hypoxic ECs. We show that PAR-2-dependent HB-EGF induction was associated with increased phosphorylation of ERK1/2, and inhibition of ERK1/2 phosphorylation attenuated PAR-2-dependent HB-EGF induction as well as EC activation. Tissue factor (TF), i.e., the major initiator of coagulation-dependent PAR signaling, was substantially induced by hypoxia in several types of cancer cells, including glioblastoma; however, TF was undetectable in ECs even at prolonged hypoxia, which precludes cell-autonomous PAR-2 activation through TF. Interestingly, hypoxic cancer cells were shown to release substantial amounts of TF that was mainly associated with secreted microvesicles with exosome-like characteristics. Vesicles derived from glioblastoma cells were found to trigger TF/VIIa-dependent activation of hypoxic ECs in a paracrine manner. We provide evidence of a hypoxia-induced signaling axis that links coagulation activation in cancer cells to PAR-2-mediated activation of ECs. The identified pathway may constitute an interesting target for the development of additional strategies to treat aggressive brain tumors.
15.	Lagging, Martin, 1965, et al. (författare) Treatment of hepatitis C virus infection in adults and children: Updated Swedish consensus recommendations 2012 Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 44:7, s. 502-521 Tidskriftsartikel (refereegranskat)abstract Swedish recommendations for the treatment of hepatitis C virus (HCV) infection were updated at a recent expert meeting. Therapy for acute HCV infection should be initiated if spontaneous resolution does not occur within 12 weeks. The recommended standard-of-care therapy for chronic HCV genotype 1 infection is an HCV protease inhibitor in combination with peginterferon (peg-IFN) and ribavirin. Treatment is strongly recommended in patients with bridging fibrosis and cirrhosis, whereas in patients with less advanced fibrosis, deferring therapy may be preferential in light of likely therapeutic improvements in the near future. Patients with chronic genotype 2/3 infection should generally be treated with peg-IFN and ribavirin for 24 weeks. In patients with a very rapid viral response (i.e. HCV RNA below 1000 IU/ml on day 7), or favourable baseline characteristics and undetectable HCV RNA week 4, treatment can be shortened to 12 - 16 weeks, provided that no dose reductions are needed.
16.	Olander, Agnes, et al. (författare) Prehospital characteristics among patients with sepsis: a comparison between patients with or without adverse outcome 2019 Ingår i: Bmc Emergency Medicine. - : Springer Science and Business Media LLC. - 1471-227X. ; 19:1 Tidskriftsartikel (refereegranskat)abstract Background The prehospital care of patients with sepsis are commonly performed by the emergency medical services. These patients may be critically ill and have high in-hospital mortality rates. Unfortunately, few patients with sepsis are identified by the emergency medical services, which can lead to delayed treatment and a worse prognosis. Therefore, early identification of patients with sepsis is important, and more information about the prehospital characteristics that can be used to identify these patients is needed. Based on this lack of information, the objectives of this study were to investigate the prehospital characteristics that are identified while patients with sepsis are being transported to the hospital by the emergency medical services, and to compare these values to those of the patients with and without adverse outcomes during their hospital stays. Methods This was a retrospective observational study. The patients' electronic health records were reviewed and selected consecutively based on the following: retrospectively diagnosed with sepsis and transported to an emergency department by the emergency medical services. Data were collected on demographics, prehospital characteristics and adverse outcomes, defined as the in-hospital mortality or treatment in the intensive care unit, and analysed by independent sample t-test and chi-square. Sensitivity, specificity and likelihood ratio, of prehospital characteristics for predicting or development of adverse outcome were analysed. Results In total, 327 patients were included. Of these, 50 patients had adverse outcomes. When comparing patients with or without an adverse outcome, decreased oxygen saturation and body temperature, increased serum glucose level and altered mental status during prehospital care were found to be associated with an adverse outcome. Conclusions The findings suggests that patients having a decreased oxygen saturation and body temperature, increased serum glucose level and altered mental status during prehospital care are at risk of a poorer patient prognosis and adverse outcome. Recognizing these prehospital characteristics may help to identify patients with sepsis early and improve their long-term outcomes. However further research is required to predict limit values of saturation and serum glucose and to validate the use of prehospital characteristics for adverse outcome in patients with sepsis.
17.	Tång Hallbäck, Erika, 1973, et al. (författare) Outbreak of OXA-48-producing Enterobacteriaceae in a neonatal intensive care unit in Western Sweden 2023 Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 1435-4373 .- 0934-9723. ; 42:5, s. 597-605 Tidskriftsartikel (refereegranskat)abstract In 2015, an outbreak caused by OXA-48-producing Enterobacteriaceae affected a neonatal intensive care unit at a Swedish University Hospital. The aim was to explore the transmission of OXA-48-producing strains between infants and the transfer of resistance plasmids between strains during the outbreak. Twenty-four outbreak isolates from ten suspected cases were whole-genome sequenced. A complete assembly was created for the index isolate (Enterobacter cloacae) and used as a mapping reference to detect its plasmids in the remaining isolates (17 Klebsiella pneumoniae, 4 Klebsiella aerogenes, and 2 Escherichia coli). Strain typing was performed using core genome MLST and SNP analysis. As judged from sequencing and clinical epidemiological data, the outbreak involved nine cases (two developed sepsis) and four OXA-48-producing strains: E. cloacae ST1584 (index case), K. pneumoniae ST25 (eight cases), K. aerogenes ST93 (two cases), and E. coli ST453 (2 cases). Two plasmids from the index strain, pEclA2 and pEclA4, carrying blaOXA48 and blaCMY-4, respectively, were traced to all K. pneumoniae ST25 isolates. Klebsiella aerogenes ST93 and E. coli ST453 harboured either only pEclA2, or both pEclA2 and pEclA4. One suspected case harbouring OXA-162-producing K. pneumoniae ST37 could be excluded from the outbreak. Once initiated by an E. cloacae strain, the outbreak was caused by the dissemination of a K. pneumoniae ST25 strain and involved inter-species horizontal transfer of two resistance plasmids, one of which carried blaOXA-48. To our knowledge, this is the first description of an outbreak of OXA-48-producing Enterobacteriaceae in a neonatal setting in northern Europe.
18.	Anesäter, Erik, et al. (författare) The influence on wound contraction and fluid evacuation of a rigid disc inserted to protect exposed organs during negative pressure wound therapy. 2011 Ingår i: International Wound Journal. - 1742-481X. ; 8, s. 393-399 Tidskriftsartikel (refereegranskat)abstract The use of a rigid disc as a barrier between the wound bed and the wound filler during negative pressure wound therapy (NPWT) has been suggested to prevent damage to exposed organs. However, it is important to determine that the effects of NPWT, such as wound contraction and fluid removal, are maintained during treatment despite the use of a barrier. This study was performed to examine the effect of NPWT on wound contraction and fluid evacuation in the presence of a rigid disc. Peripheral wounds were created on the backs of eight pigs. The wounds were filled with foam, and rigid discs of different designs were inserted between the wound bed and the foam. Wound contraction and fluid evacuation were measured after application of continuous NPWT at -80 mmHg. Wound contraction was similar in the presence and the absence of a rigid disc (84 ± 4% and 83 ± 3%, respectively, compared with baseline). Furthermore, the rigid disc did not affect wound fluid removal compared with ordinary NPWT (e.g. after 120 seconds, 71 ± 4 ml was removed in the presence and 73 ± 3 ml was removed in the absence of a disc). This study shows that a rigid barrier may be placed under the wound filler to protect exposed structures during NPWT without affecting wound contraction and fluid removal, which are two crucial features of NPWT.
19.	Johansson Kostenniemi, Urban, 1987-, et al. (författare) MeningiSSS : A New Predictive Score to Support Decision on Invasive Procedures to Monitor or Manage the Intracerebral Pressure in Children with Bacterial Meningitis 2020 Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 32:2, s. 586-595 Tidskriftsartikel (refereegranskat)abstract Background: Knowing the individual child’s risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors.Methods: We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure.Results: For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p < 0.01). For intensive care, the MeningiSSS (AUC = 0.79) and the Simple Luanda Scale (AUC = 0.75) had the best results in the ROC-analysis, whereas others performed less well (AUC ≤ 0.65). Finally, while none of the scores’ results were significantly associated with complications, an elevated score on the MeningiSSS (AUC = 0.70), Niklasson Scale (AUC = 0.72), and the Herson–Todd Scale (AUC = 0.79) was all associated with death.Conclusions: The MeningiSSS outperformed existing predictive scores at identifying children later having to undergo invasive procedures to monitor or manage the intracerebral pressure in children with bacterial meningitis. Our results need further external validation before use in clinical practice. Thus, the MeningiSSS could potentially be helpful when making difficult decisions concerning intracerebral pressure management.
20.	Orfanos, Ioannis, et al. (författare) Paediatric emergency departments should manage young febrile and afebrile infants the same if they have a fever before presenting 2022 Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:10 Tidskriftsartikel (refereegranskat)abstract Aim Our aim was to evaluate the risk of bacterial meningitis, bacteremia, and urinary tract infection (UTI) in infants <= 60 days who presented to paediatric emergency departments (PEDs) after having fever at home. We also investigated any differences between infants who were afebrile or febrile on presentation. Methods This was a multicenter retrospective study of infants <= 60 days presented to four Swedish PEDs during 2014-2020 with reported fever at home. We used relative risks (RR) to compare the prevalence of UTI, bacteremia, and bacterial meningitis between the infants who were afebrile and the infants who were still febrile when they presented to the PED. Results The cohort comprised 1926 infants, and 702 (36%) were afebrile on presentation. The prevalence of UTI in the afebrile and febrile infants was 6.1% [95% confidence interval (CI) 4.5-8.2] versus 14.2% (95% CI 12.3-16.2), corresponding to an RR of 0.43 (95% CI 0.31-0.59). In infants <= 28 days, the RR for meningitis was 1.05 (95% CI 0.18-6.23) for afebrile versus febrile infants. Five times more febrile infants underwent a lumbar puncture. Conclusion Infants who were afebrile on presentation underwent fewer lumbar punctures, but they had similar rates of bacterial meningitis to febrile infants. Different management approaches are not justified.
21.	Sundvall, Pär-Daniel, et al. (författare) Evaluation of dipstick analysis among elderly residents to detect bacteriuria: a cross-sectional study in 32 nursing homes. 2009 Ingår i: BMC geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 9 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Few studies have evaluated dipstick urinalysis for elderly and practically none present confidence intervals. Furthermore, most previous studies combine all bacteria species in a "positive culture". Thus, their evaluation may be inappropriate due to Yule-Simpson's paradox. The aim of this study was to evaluate diagnostic accuracy of dipstick urinalysis for the elderly in nursing homes. METHODS: In this cross-sectional study voided urine specimens were collected from 651 elderly individuals in nursing homes. Dipstick urinalysis for nitrite, leukocyte esterase and urine culture were performed. Sensitivity, specificity, positive and negative predictive values with 95% confidence intervals were calculated. Visual readings were compared to readings with a urine chemistry analyzer. RESULTS: 207/651 (32%) of urine cultures showed growth of a potentially pathogenic bacterium. Combining the two dipsticks improved test characteristics slightly compared to using only one of the dipsticks. When both dipsticks are negative, presence of potentially pathogenic bacteria can be ruled out with a negative predictive value of 88 (84-92)%. Visual and analyzer readings had acceptable agreement. CONCLUSION: When investigating for bacteriuria in elderly people at nursing homes we suggest nitrite and leukocyte esterase dipstick be combined. There are no clinically relevant differences between visual and analyzer dipstick readings. When dipstick urinalysis for nitrite and leukocyte esterase are both negative it is unlikely that the urine culture will show growth of potentially pathogenic bacteria and in a patient with an uncomplicated illness further testing is unnecessary.
22.	Sundvall, Pär-Daniel, et al. (författare) Interleukin-6 concentrations in the urine and dipstick analyses were related to bacteriuria but not symptoms in the elderly: a cross sectional study of 421 nursing home residents 2014 Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 14 Tidskriftsartikel (refereegranskat)abstract Background: Up to half the residents of nursing homes for the elderly have asymptomatic bacteriuria (ABU), which should not be treated with antibiotics. A complementary test to discriminate between symptomatic urinary tract infections (UTI) and ABU is needed, as diagnostic uncertainty is likely to generate significant antibiotic overtreatment. Previous studies indicate that Interleukin-6 (IL-6) in the urine might be suitable as such a test. The aim of this study was to investigate the association between laboratory findings of bacteriuria, IL-6 in the urine, dipstick urinalysis and newly onset symptoms among residents of nursing homes. Methods: In this cross sectional study, voided urine specimens for culture, urine dipstick and IL-6 analyses were collected from all residents capable of providing a voided urine sample, regardless of the presence of symptoms. Urine specimens and symptom forms were provided from 421 residents of 22 nursing homes. The following new or increased nonspecific symptoms occurring during the previous month were registered; fatigue, restlessness, confusion, aggressiveness, loss of appetite, frequent falls and not being herself/himself, as well as symptoms from the urinary tract; dysuria, urinary urgency and frequency. Results: Recent onset of nonspecific symptoms was common among elderly residents of nursing homes (85/421). Urine cultures were positive in 32% (135/421), Escherichia coli was by far the most common bacterial finding. Residents without nonspecific symptoms had positive urine cultures as often as those with nonspecific symptoms with a duration of up to one month. Residents with positive urine cultures had higher concentrations of IL-6 in the urine (p < 0.001). However, among residents with positive urine cultures there were no differences in IL-6 concentrations or dipstick findings between those with or without nonspecific symptoms. Conclusions: Nonspecific symptoms among elderly residents of nursing homes are unlikely to be caused by bacteria in the urine. This study could not establish any clinical value of using dipstick urinalysis or IL-6 in the urine to verify if bacteriuria was linked to nonspecific symptoms.
23.	Kechagias, KS, et al. (författare) Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: systematic review and meta-analysis 2022 Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833. ; 378 Tidskriftsartikel (refereegranskat)abstract To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment.DesignSystematic review and meta-analysisData sourcesPubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov were screened from inception to 31 March 2021.Review methodsStudies reporting on the risk of HPV infection and recurrence of disease related to HPV infection after local surgical treatment of preinvasive genital disease in individuals who were vaccinated were included. The primary outcome measure was risk of recurrence of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) after local surgical treatment, with follow-up as reported by individual studies. Secondary outcome measures were risk of HPV infection or other lesions related to HPV infection. Independent and in duplicate data extraction and quality assessment were performed with ROBINS-I and RoB-2 tools for observational studies and randomised controlled trials, respectively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was implemented for the primary outcome. Observational studies and randomised controlled trials were analysed separately from post hoc analyses of randomised controlled trials. Pooled risk ratios and 95% confidence intervals were calculated with a random effects meta-analysis model. The restricted maximum likelihood was used as an estimator for heterogeneity, and the Hartung-Knapp-Sidik-Jonkman method was used to derive confidence intervals.Results22 articles met the inclusion criteria of the review; 18 of these studies also reported data from a non-vaccinated group and were included in the meta-analyses (12 observational studies, two randomised controlled trials, and four post hoc analyses of randomised controlled trials). The risk of recurrence of CIN2+ was reduced in individuals who were vaccinated compared with those who were not vaccinated (11 studies, 19 909 participants; risk ratio 0.43, 95% confidence interval 0.30 to 0.60; I2=58%, τ2=0.14, median follow-up 36 months, interquartile range 24-43.5). The effect estimate was even stronger when the risk of recurrence of CIN2+ was assessed for disease related to HPV subtypes HPV16 or HPV18 (six studies, 1879 participants; risk ratio 0.26, 95% confidence interval 0.16 to 0.43; I2=0%, τ2=0). Confidence in the meta-analysis for CIN2+ overall and CIN2+ related to HPV16 or HPV18, assessed by GRADE, ranged from very low to moderate, probably because of publication bias and inconsistency in the studies included in the meta-analysis. The risk of recurrence of CIN3 was also reduced in patients who were vaccinated but uncertainty was large (three studies, 17 757 participants; 0.28, 0.01 to 6.37; I2=71%, τ2=1.23). Evidence of benefit was lacking for recurrence of vulvar, vaginal, and anal intraepithelial neoplasia, genital warts, and persistent and incident HPV infections, although the number of studies and participants in each outcome was low.ConclusionHPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision. GRADE assessment for the quality of evidence indicated that the data were inconclusive. Large scale, high quality randomised controlled trials are required to establish the level of effectiveness and cost of HPV vaccination in women undergoing treatment for diseases related to HPV infection.Systematic review registrationPROSPERO CRD42021237350.
24.	Peters, Lynn, et al. (författare) Multiple antibiotic resistance as a risk factor for mortality and prolonged hospital stay: A cohort study among neonatal intensive care patients with hospital-acquired infections caused by gram-negative bacteria in Vietnam 2019 Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:5 Tidskriftsartikel (refereegranskat)abstract Background Antibiotic resistance (ABR) is an increasing burden for global health. The prevalence of ABR in Southeast Asia is among the highest worldwide, especially in relation to hospital acquired infections (HAI) in intensive care units (ICU). However, little is known about morbidity and mortality attributable to ABR in neonates. Aim This study aimed to assess mortality and the length of hospitalization attributable to ABR in gram-negative bacteria (GNB) causing HAI in a Vietnamese neonatal ICU (NICU). Methods We conducted a prospective cohort study (n = 296) in a NICU in Hanoi, Vietnam, from March 2016 to October 2017. Patients isolated with HAI caused by GNB were included. The exposure was resistance to multiple antibiotic classes, the two outcomes were mortality and length of hospital stay (LOS). Data were analysed using two regression models, controlling for confounders and effect modifiers such as co-morbidities, time at risk, severity of illness, sex, age, and birthweight. Results The overall case fatality rate was 44.3% and the 30 days mortality rate after infection was 31.8%. For every additional resistance to an antibiotic class, the odds of a fatal outcome increased by 27% and LOS increased by 2.1 days. These results were statistically significant (p amp;lt; 0.05). Conclusion ABR was identified as a significant risk factor for adverse outcomes in neonates with HAI. These findings are generally in line with previous research in children and adults. However, heterogeneous study designs, the neglect of important confounders and varying definitions of ABR impair the validity, reliability, and comparability of results.
25.	Hesse, Camilla, et al. (författare) The N-terminal domain of α-dystroglycan is released as a 38kDa protein and is increased in cerebrospinal fluid in patients with Lyme neuroborreliosis. 2011 Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 412:3, s. 494-499 Tidskriftsartikel (refereegranskat)abstract α-Dystroglycan is an extracellular adhesion protein that is known to interact with different ligands. The interaction is thought to stabilize the integrity of the plasma membrane. The N-terminal part of α-dystroglycan may be proteolytically processed to generate a small 38kDa protein (α-DG-N). The physiological significance of α-DG-N is unclear but has been suggested to be involved in nerve regeneration and myelination and to function as a potential biomarker for neurodegenerative and neuromuscular diseases. In this report we show that α-DG-N is released into different body fluids, such as lachrimal fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the significance of α-DG-N in CSF we examined the levels of α-DG-N and known neurodegenerative markers in CSF from patients diagnosed with Lyme neuroborreliosis (LNB) and healthy controls. In untreated acute phase LNB patients, 67% showed a significant increase of CSF α-DG-N compared to healthy controls. After treatment with antibiotics the CSF α-DG-N levels were normalized in the LNB patients.
26.	Kanberg, Nelly, et al. (författare) Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19. 2020 Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 95:12 Tidskriftsartikel (refereegranskat)abstract To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
27.	Midlöv, Patrik, et al. (författare) Medication report reduces number of medication errors when elderly patients are discharged from hospital 2008 Ingår i: PHARMACY WORLD & SCIENCE. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 30:1, s. 92-98 Tidskriftsartikel (refereegranskat)abstract Objective To investigate whether a Medication Report can reduce the number of medication errors when elderly patients are discharged from hospital. Method We conducted a prospective intervention with retrospective controls on patients at three departments at Lund University Hospital, Sweden that where transferred to primary care. The intervention group, where patients received a Medication Report at discharge, was compared with a control group with patients of the same age, who were not given a Medication Report when discharged from the same ward one year earlier. Main outcome measures The main outcome measure was the number of medication errors when elderly patients were discharged from hospital. Results Among 248 patients in the intervention group 79 (32%) had at least one medication error as compared with 118 (66%) among the 179 patients in the control group. In the intervention group 15% of the patients had errors that were considered to have moderate or high risk of clinical consequences compared with 32% in the control group. The differences were statistically significant (P < 0.001). Conclusion Medication errors are common when elderly patients are discharged from hospital. The Medication Report is a simple tool that reduces the number of medication errors.
28.	Arabpour, Mohammad, et al. (författare) ADP-ribosylating adjuvant reveals plasticity in cDC1 cells that drive mucosal Th17 cell development and protection against influenza virus infection 2022 Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 15:4, s. 745-761 Tidskriftsartikel (refereegranskat)abstract Migratory dendritic cells expressing CD103 are the targets for mucosal vaccines. These belong to either of two lineage-restricted subsets, cDC1 or cDC2 cells, which have been linked to priming of functionally distinct CD4 T cells. However, recent studies have identified plasticity in cDC2 cells with overlapping functions with cDC1 cells, while the converse has not been reported. We genetically engineered a vaccine adjuvant platform that targeted the cholera toxin A1 (CTA1) ADP-ribosylating enzyme to CD103(+) cDC1 and cDC2 cells using a single-chain antibody (scFv) to CD103. Unexpectedly, intranasal immunization with the CTA1-svFcCD103 adjuvant modified cDC1 cells to effectively prime Th17 cells, a function previously limited to cDC2 cells. In fact, cDC2 cells were dispensible, while cDC1 cells, lacking in Batf3-/- mice, were critical. Following intranasal immunizations isolated cDC1 cells from mLN exclusively promoted Rorgt(+) T cells and IL-17, IL-21, and IL-22 production. Strong CD8 T cell responses through antigen cross presentation by cDC1 cells were also observed. Single-cell RNAseq analysis revealed upregulation of Th17-promoting gene signatures in sorted cDC1 cells. Gene expression in isolated cDC2 cells was largely unaffected. Our finding represents a major shift of paradigm as we have documented functional plasticity in cDC1 cells.
29.	Sourander, Birger, et al. (författare) No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study 2022 Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 54:10, s. 703-712 Tidskriftsartikel (refereegranskat)abstract Background The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. Methods We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher's exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. Results We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. Conclusions Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.
30.	Cedergren Weber, Gustav, et al. (författare) The Impact of COVID-19 on Parkinson's Disease : A Case-Controlled Registry and Questionnaire Study on Clinical Markers and Patients' Perceptions 2023 Ingår i: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 2023 Tidskriftsartikel (refereegranskat)abstract Introduction: Parkinson's disease (PD) is a neurodegenerative disease with motor and nonmotor symptoms. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Objectives: To explore how COVID-19 affects motor, nonmotor, and general health aspects of PD and to map how PD patients perceive their change in symptoms since falling ill with COVID-19.Method: The study was descriptive, case-controlled, and based on both registry and questionnaire data. At baseline, the controls were matched on age, sex, and disease severity. Information on the severity of the disease, nonmotor symptoms, motor symptoms, and general health was retrieved from the Swedish Registry for PD. Registry data from a COVID-19 group (n=45) and a control group (n=73), as well as questionnaires from a COVID-19 group (n=24) and a control group (n=42), were compared.Results: We did not find that SARS-CoV-2 infection affects any major aspect of nonmotor symptoms, motor symptoms, general health, and perception of change in PD patients' post-COVID-19. Compared to controls, the COVID-19 group reported a more positive subjective experience of pain and quality of life and a perception of change post-COVID-19 regarding general motor function, sleep quality, and mood (all p<0.05).Conclusion: Although SARS-CoV-2 infection does not seem to affect PD symptoms in any major respect, the subjective experience of several aspects of life in PD patients might be slightly improved post-COVID-19 compared to a control group. The findings warrant further investigations due to the small sample size and possible survivorship bias.
31.	Arirachakaran, Pratanporn, et al. (författare) Highly-active antiretroviral therapy and oral opportunistic microorganisms in HIV-positive individuals of Thailand. 2016 Ingår i: Journal of investigative and clinical dentistry. - : Wiley. - 2041-1626 .- 2041-1618. ; 7:2, s. 158-167 Tidskriftsartikel (refereegranskat)abstract Oral mucosal lesions and opportunistic microorganisms in HIV-positive Thais treated with highly-active antiretroviral therapy (HAART) for more than 5years were investigated.
32.	Hammarström, Helena, et al. (författare) Prospective evaluation of a combination of fungal biomarkers for the diagnosis of invasive fungal disease in high-risk haematology patients 2018 Ingår i: Mycoses. - : Wiley. - 0933-7407 .- 1439-0507. ; 61:9, s. 623-632 Tidskriftsartikel (refereegranskat)abstract We prospectively evaluated a combination of fungal biomarkers in adult haematology patients with focus on their clinical utility at different time points during the course of infection. In total, 135 patients were monitored once to twice weekly for serum (1-3)-ß-d-glucan (BG), galactomannan (GM), bis-methyl-gliotoxin and urinary d-arabinitol/l-arabinitol ratio. In all, 13 cases with proven or probable invasive fungal disease (IFD) were identified. The sensitivity of BG and GM at the time of diagnosis (TOD) was low, but within 2 weeks from the TOD the sensitivity of BG was 92%. BG >800 pg/mL was highly specific for IFD. At a pre-test probability of 12%, both BG and GM had negative predictive values (NPV) >0.9 but low positive predictive values (PPV). In a subgroup analysis of patients with clinically suspected IFD (pre-test probability of 35%), the NPV was lower, but the PPV for BG was 0.86 at cut-off 160 pg/mL. Among IFD patients, 91% had patterns of consecutively positive and increasing BG levels. Bis-methyl-gliotoxin was undetectable in 15 patients with proven, probable and possible IA. To conclude, BG was the superior fungal marker for IFD diagnosis. Quantification above the limit of detection and graphical evaluation of the pattern of dynamics are warranted in the interpretation of BG results.
33.	Johansson, Inger, 1953, et al. (författare) Lower incidence of CMV infection and acute rejections with valganciclovir 2013 Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 13 Tidskriftsartikel (refereegranskat)abstract Background Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS).Finding a strategy to prevent CMV infection is an important issue. Methods We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed. Results For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival. For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%). Conclusions A lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival.
34.	Klaric, Lucija, et al. (författare) Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19. 2021 Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28 Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
35.	Klingspor, L., et al. (författare) Epidemiology of fungaemia in Sweden: A nationwide retrospective observational survey 2018 Ingår i: Mycoses. - : Wiley. - 0933-7407 .- 1439-0507. ; 61:10, s. 777-785 Tidskriftsartikel (refereegranskat)abstract ObjectivesTo identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates to identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates in Sweden. MethodsThe study was a retrospective, observational nationwide laboratory-based surveillance for fungaemia and fungal meningitis and was conducted from September 2015 to August 2016. ResultsIn total, 488 Candida blood culture isolates were obtained from 471 patients (58% males). Compared to our previous study, the incidence of candidaemia has increased from 4.2/100000 (2005-2006) to 4.7/100000 population/year (2015-2016). The three most common Candida spp. isolated from blood cultures were Candida albicans (54.7%), Candida glabrata (19.7%) and species in the Candida parapsilosis complex (9.4%). Candida resistance to fluconazole was 2% in C.albicans and between 0% and 100%, in non-albicans species other than C.glabrata and C.krusei. Resistance to voriconazole was rare, except for C.glabrata, C.krusei and C.tropicalis. Resistance to anidulafungin was 3.8% while no Candida isolate was resistant to amphotericin B. ConclusionsWe report an overall increase in candidaemia but a minor decrease of C.albicans while C.glabrata and C.parapsilosis remain constant over this 10-year period.
36.	Oltean, Mihai, 1976, et al. (författare) Covid-19 in kidney transplant recipients: a systematic review of the case series available three months into the pandemic. 2020 Ingår i: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 52:11, s. 830-7 Tidskriftsartikel (refereegranskat)abstract Coronavirus disease 2019 (COVID-19) ranges from a mild illness to acute respiratory distress syndrome (ARDS), multiorgan dysfunction, and death. Transplant recipients are vulnerable due to comorbidities and immunosuppressants that render them susceptible to infections. The information on COVID-19 in kidney transplant recipients remains limited to small case series.A systematic literature search was conducted, and 12 case series totalling 204 kidney transplant recipients with COVID-19 were identified. Data were extracted, pooled and analysed.Most patients (74%) were men. The most frequent symptoms were fever (76%), cough (64%) and dyspnoea (43%). At admission, over 70% of the patients had abnormal radiological findings. Leukocyte counts were in the lower normal range. C-reactive protein, ferritin, and D-dimer were consistently increased. Treatments included lowering immunosuppression, hydroxychloroquine, antivirals, tocilizumab and intravenous immunoglobulins. Thirty-one percent of the patients were admitted to intensive care units (ICUs), and 16% required intubation. The overall mortality was 21.2%. Patients who died were significantly older than those who survived (61±12 vs. 51±15, p<.01). Logistic regression revealed that the odds for death increased by 4.3% for each additional year of age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.005-1.083, p value=.0265).No substantial conclusions could be drawn on the efficacy of any particular treatment. More rigorous patient stratification is needed when analysing and reporting data to facilitate future meta-analyses.
37.	Rhedin, Samuel, et al. (författare) Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children- The TREND study 2022 Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 28:9, s. 1251-1257 Tidskriftsartikel (refereegranskat)abstract Objective: Discriminating between viral and bacterial lower respiratory tract infection (LRTI) in children is challenging, leading to an excessive use of antibiotics. Myxovirus resistance protein A (MxA) is a promising biomarker for viral infections. The primary aim of the study was to assess differences in blood MxA levels between children with viral and bacterial LRTI. Secondary aims were to assess differences in blood MxA levels between children with viral LRTI and asymptomatic controls and to assess MxA levels in relation to different respiratory viruses. Methods: Children with LRTI were enrolled as cases at Sachs' Children and Youth Hospital, Stockholm, Sweden. Nasopharyngeal aspirates and blood samples for analysis of viral PCR, MxA, and C-reactive protein were systematically collected from all study subjects in addition to standard laboratory/radiology assessment. Aetiology was defined according to an algorithm based on laboratory and radiological findings. Asymptomatic children with minor surgical disease were enrolled as controls. Results: MxA levels were higher in children with viral LRTI (n = 242) as compared to both bacterial (n = 5) LRTI (p < 0.01, area under the curve (AUC) 0.90, 95% CI: 0.81 to 0.99), and controls (AUC 0.92, 95% CI: 0.88 to 0.95). In the subgroup of children with pneumonia diagnosis, a cutoff of MxA 430 mg/l discriminated between viral (n = 29) and bacterial (n = 4) aetiology with 93% (95% CI: 78-99%) sensi-tivity and 100% (95% CI: 51-100%) specificity (AUC 0.98, 95% CI: 0.94 to 1.00). The highest MxA levels were seen in cases PCR positive for influenza (median MxA 1699 mg/l, interquartile range: 732 to 2996) and respiratory syncytial virus (median MxA 1115 mg/l, interquartile range: 679 to 2489). Discussion: MxA accurately discriminated between viral and bacterial aetiology in children with LRTI, particularly in the group of children with pneumonia diagnosis, but the number of children with bacterial LRTI was low.
38.	Sandström, Göran, et al. (författare) Helicobacter pylori Antibodies and Iron Deficiency in Female Adolescents. 2014 Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11 Tidskriftsartikel (refereegranskat)abstract Iron deficiency (ID) is a common clinical problem worldwide, affecting primarily females. Helicobacter pylori (HP) infection has been shown to be associated with ID. The objective of this study was to define the prevalence of HP antibodies in female adolescents, and to find out if there was a correlation between HP infection and ID. The secondary aim was to study if regularly performed sporting activity, have any association to HP infection, in itself.
39.	Skogman, Barbro H., et al. (författare) The NeBoP score : a clinical prediction test for evaluation of children with Lyme Neuroborreliosis in Europe 2015 Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 15 Tidskriftsartikel (refereegranskat)abstract Background: The diagnosis of Lyme neuroborreliosis (LNB) in Europe is based on clinical symptoms and laboratory data, such as pleocytosis and anti-Borrelia antibodies in serum and CSF according to guidelines. However, the decision to start antibiotic treatment on admission cannot be based on Borrelia serology since results are not available at the time of lumbar puncture. Therefore, an early prediction test would be useful in clinical practice. The aim of the study was to develop and evaluate a clinical prediction test for children with LNB in a relevant European setting. Method: Clinical and laboratory data were collected retrospectively from a cohort of children being evaluated for LNB in Southeast Sweden. A clinical neuroborreliosis prediction test, the NeBoP score, was designed to differentiate between a high and a low risk of having LNB. The NeBoP score was then prospectively validated in a cohort of children being evaluated for LNB in Central and Southeast Sweden (n = 190) and controls with other specific diagnoses (n = 49). Results: The sensitivity of the NeBoP score was 90 % (CI 95 %; 82-99 %) and the specificity was 90 % (CI 95 %; 85-96 %). Thus, the diagnostic accuracy (i.e. how the test correctly discriminates patients from controls) was 90 % and the area under the curve in a ROC analysis was 0.95. The positive predictive value (PPV) was 0.83 (CI 95 %; 0.75-0.93) and the negative predictive value (NPV) was 0.95 (CI 95 %; 0.90-0.99). Conclusion: The overall diagnostic performance of the NeBoP score is high (90 %) and the test is suggested to be useful for decision-making about early antibiotic treatment in children being evaluated for LNB in European Lyme endemic areas.
40.	Söfteland, John M., 1977, et al. (författare) COVID-19 in solid organ transplant recipients : A national cohort study from Sweden 2021 Ingår i: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 21:8, s. 2762-2773 Tidskriftsartikel (refereegranskat)abstract Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1-2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6-7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.
41.	Birindwa, Archippe M., et al. (författare) Decreased number of hospitalized children with severe acute lower respiratory infection after introduction of the pneumococcal conjugate vaccine in the Eastern Democratic Republic of the Congo. 2020 Ingår i: Pan African Medical Journal. - : Pan African Medical Journal. - 1937-8688. ; 37 Tidskriftsartikel (refereegranskat)abstract Introduction: acute lower respiratory infections (ALRI) are a leading killer of children under five worldwide including the Democratic Republic of the Congo (DR Congo). We aimed to determine the morbidity and case fatality rate due to ALRI before and after introduction of the 13-valent pneumococcal conjugate vaccine (PVC13) in DR Congo 2013. Methods: data were collected from medical records of children with a diagnosis of ALRI, aged from 2 to 59 months, treated at four hospitals in the eastern DR Congo. Two study periods were defined; from 2010 to 2012 (before introduction of PCV13) and from 2014 to 2015 (after PCV13 introduction). Results: out of 21,478 children admitted to the hospitals during 2010-2015, 2,007 were treated for ALRI. The case fatality rate among these children was 4.9%. Death was significantly and independently associated with malnutrition, severe ALRI, congenital disease and symptoms of fatigue. Among the ALRI hospitalised children severe ALRI decreased from 31% per year to 18% per year after vaccine introduction (p = 0.0002) while the fatality rate remained unchanged between the two study periods. Following introduction of PCV13, 63% of the children diagnosed with ALRI were treated with ampicillin combined with gentamicin while 33% received ceftriaxone and gentamicin. Conclusion: three years after PCV13 introduction in the Eastern part of the DR Congo, we found a reduced risk of severe ALRI among children below five years. Broad-spectrum antibiotics were frequently used for the treatment of ALRI in the absence of any microbiological diagnostic support.
42.	Bergthorsdottir, Ragnhildur, 1971, et al. (författare) Increased risk of hospitalization, intensive care and death due to covid-19 in patients with adrenal insufficiency : a Swedish nationwide study 2024 Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 295:3, s. 322-330 Tidskriftsartikel (refereegranskat)abstract Background: Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown.Methods: In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis.Results: We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59–2.43), intensive care admission (2.76, 1.49–5.09) and death (2.29, 1.60–3.28).Conclusion: Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.
43.	Waldenström, Jesper, 1985, et al. (författare) The relation of 25-hydroxy vitamin D concentrations to liver histopathology, seasonality and baseline characteristics in chronic hepatitis C virus genotype 2 or 3 infection 2020 Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:8 Tidskriftsartikel (refereegranskat)abstract Background and objectives The hydroxylation to 25-hydroxy vitamin D (25(OH)D) occurs in the liver and the impact of liver disease on vitamin D is unclear. This study evaluated the relationship between vitamin D concentrations and hepatic histopathology, seasonality and patient characteristics in well-characterized patients having undergone a liver biopsy. Method 25(OH)D was measuredpost-hocin pre-treatment serum from 331 North European patients with chronic HCV genotype 2 or 3 infection (NORDynamIC study). Liver biopsies were scored for fibrosis and inflammation according to the Ishak protocol, and graded for steatosis. Non-invasive markers of hepatic fibrosis as well as baseline viral and host characteristics, including genetic polymorphisms rs2228570, rs7975232, and rs10877012 were also evaluated. Results Mean 25(OH)D concentration was 59 +/- 23 nmol/L, with 41% having values <50 nmol/L and 6% were <30 nmol/L. 25(OH)D correlated with fibrosis (r = -0.10, p <= 0.05) in univariate but not in multivariate analyses. No association was observed between 25(OH)D and hepatic inflammation, but with steatosis in HCV genotype 2 infected patients. None of the genetic polymorphisms impacted on 25(OH)D levels or fibrosis. 25(OH)D levels were significantly inversely correlated to BMI (r = -0.19, p = 0.001), and was also associated with season and non-Caucasian ethnicity. Conclusion Fibrosis was not independently associated with 25(OH)D concentration and no association was seen with hepatic inflammation, but HCV genotype 2 infected patients with moderate-to-severe steatosis had lower 25(OH)D levels compared to those without steatosis. A high percentage had potential risk of 25(OH)D deficiency, and BMI, seasonality and ethnicity were independently associated with 25(OH)D as previously reported.
44.	Butler, C. C., et al. (författare) Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial 2020 Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 395:10217, s. 42-52 Tidskriftsartikel (refereegranskat)abstract Background Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. Methods We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. Findings Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1.29, 95% Bayesian credible interval [BCrI] 1.20-1.39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1.13 to 1.72. The estimated absolute mean benefit from oseltamivir was 1.02 days (95% [BCrI] 0.74-1.31) overall, and in the prespecified subgroups, ranged from 0.70 (95% BCrI 0.30-1.20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3.20 (95% BCrI 1.00-5.50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. Interpretation Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
45.	Wanat, M., et al. (författare) Supporting Primary Care Professionals to Stay in Work During the COVID-19 Pandemic: Views on Personal Risk and Access to Testing During the First Wave of Pandemic in Europe 2021 Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8 Tidskriftsartikel (refereegranskat)abstract Background: Minimising primary care professionals' (PCPs) risk of SARS-CoV-2 infection is crucial to ensure their safety as well as functioning health care system. PCPs' perspectives on the support they needed in the early stages of a public health crisis can inform future preparedness. Aim: To understand PCPs' experiences of providing care during the COVID-19 pandemic, with focus on personal risk from COVID-19 and testing. Design and Setting: Qualitative study using semi-structured interviews with PCPs in England, Belgium, the Netherlands, Ireland, Germany, Poland, Greece and Sweden, between April and July 2020. Method: Interviews were analysed using a combination of inductive and deductive thematic analysis techniques. Results: Eighty interviews were conducted, showing that PCPs tried to make sense of their risk of both contracting and severity of COVID-19 by assessing individual risk factors and perceived effectiveness of Personal Protective Equipment (PPE). They had limited access to PPE yet continued providing care as their "duty." Some PCPs felt that they were put in high-risk situations when patients or colleagues were not flagging symptoms of COVID-19. Not having access to testing in the initial stages of the pandemic was somewhat accepted but when available, was valued. Conclusion: Access to adequate PPE and testing, as well as training for staff and education for patients about the importance of ensuring staff safety is crucial. Given PCPs' varied response in how they appraised personal risk and their tolerance for working, PCPs may benefit from the autonomy in deciding how they want to work during health emergencies.
46.	Larsson, Alexandra C, 1986, et al. (författare) Physical Function, Cognitive Function, and Daily Activities in Patients Hospitalized Due to COVID-19 : A Descriptive Cross-Sectional Study in Sweden. 2021 Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:21 Tidskriftsartikel (refereegranskat)abstract An estimated 14-20% of people infected with COVID-19 require medical care. The aim of the present study was to evaluate physical function, cognitive function, and daily activities in patients hospitalized due to COVID-19, and to investigate differences depending on age and admission to the intensive care unit (ICU). This prospective descriptive cross-sectional study included a consecutive sample of 211 patients (mean age 65.1 years, 67.3% men) hospitalized due to COVID-19 in Sweden. Data regarding physical function and daily activities were collected in hospital from July 2020 to February 2021. The average length of hospital stay was 33.8 days, and 48.8% of the patients were admitted to the ICU. Physical function (grip- and lower body strength) was reduced in both groups, and significantly more in the older group, ≥65 years old, compared to the younger. Furthermore, the older group also had significantly less ability to perform activities in daily life, and had significantly reduced cognitive function as compared to the younger age group. In patients treated in the ICU, physical impairments as well as the activity level were significantly more pronounced compared to patients not treated in the ICU. Patients hospitalized due to COVID-19 are physically impaired, have mild cognitive impairments, and have difficulties performing daily activities. The findings in this study indicate the need for out-patient follow-up and rehabilitation for patients hospitalized due to COVID-19, especially in older patients and patients treated in the ICU.
47.	Nordahl, Emma, et al. (författare) Domain 5 of high molecular weight kininogen is antibacterial. 2005 Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 280:41, s. 34832-34839 Tidskriftsartikel (refereegranskat)abstract Antimicrobial peptides are important effectors of the innate immune system. These peptides belong to a multifunctional group of molecules that apart from their antibacterial activities also interact with mammalian cells and glycosaminoglycans and control chemotaxis, apoptosis, and angiogenesis. Here we demonstrate a novel antimicrobial activity of the heparin-binding and cell-binding domain 5 of high molecular weight kininogen. Antimicrobial epitopes of domain 5 were characterized by analysis of overlapping peptides. A peptide, HKH20 (His(479) - His(498)), efficiently killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa and the Gram-positive Enterococcus faecalis. Fluorescence microscopy and electron microscopy demonstrated that HKH20 binds to and induces breaks in bacterial membranes. Furthermore, no discernible hemolysis or membrane-permeabilizing effects on eukaryotic cells were noted. Proteolytic degradation of high molecular weight kininogen by neutrophil-derived proteases as well as the metalloproteinase elastase from P. aeruginosa yielded fragments comprising HKH20 epitopes, indicating that kininogen-derived antibacterial peptides are released during proteolysis.
48.	Pasupuleti, Mukesh, et al. (författare) Preservation of Antimicrobial Properties of Complement Peptide C3a, from Invertebrates to Humans 2007 Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 282:4, s. 2520-2528 Tidskriftsartikel (refereegranskat)abstract The human anaphylatoxin peptide C3a, generated during complement activation, exerts antimicrobial effects. Phylogenetic analysis, sequence analyses, and structural modeling studies paired with antimicrobial assays of peptides from known C3a sequences showed that, in particular in vertebrate C3a, crucial structural determinants governing antimicrobial activity have been conserved during the evolution of C3a. Thus, regions of the ancient C3a from Carcinoscorpius rotundicauda as well as corresponding parts of human C3a exhibited helical structures upon binding to bacterial lipopolysaccharide permeabilized liposomes and were antimicrobial against Gram-negative and Gram-positive bacteria. Human C3a and C4a (but not C5a) were antimicrobial, in concert with the separate evolutionary development of the chemotactic C5a. Thus, the results demonstrate that, notwithstanding a significant sequence variation, functional and structural constraints imposed on C3a during evolution have preserved critical properties governing antimicrobial activity.
49.	Robertson, Josefina, et al. (författare) Serum neopterin levels in relation to mild and severe COVID-19 2020 Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 20:1 Tidskriftsartikel (refereegranskat)abstract Background: The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS. The aim of this study was to investigate whether serum neopterin is associated with the severity of COVID-19. Methods: We included 34 patients with confirmed COVID-19 between March 3 and March 30, 2020. Fifteen patients had mild disease and did not require hospitalization, whereas 19 patients developed severe COVID-19 requiring intensive care. Concentrations of serum neopterin, tryptophan, and kynurenine were measured at and repeatedly after inclusion. Results: We found a more than two-fold higher mean concentration of neopterin in severely ill patients (mean value 42.0 nmol/L (SD 18.2)) compared to patients with mild symptoms (16.9 nmol/L (SD 11.0)). All of the severe cases had elevated neopterin concentrations (> 9.1 nmol/L) at the initial sampling with values ranging from 17.2 to 86.7 nmol/L. In comparison, 10 of 15 patients with mild disease had neopterin levels above 9.1 nmol/L, with concentrations in the range from 4.9 to 31.6 nmol/L. Neopterin levels gradually decreased during the course of COVID-19, but severe cases maintained elevated levels for a longer period. Moreover, lower levels of tryptophan and higher levels of kynurenine, indicating an increased tryptophan catabolism, were seen in the group with severe cases. Conclusions: In conclusion, we found that serum neopterin levels are associated with the severity of COVID-19. Our findings suggest that neopterin could be used as a prognostic marker, but further studies are needed to elucidate how it can be used in the clinic.
50.	Brandström, Per, 1959, et al. (författare) The Swedish Reflux Trial in Children: III. Urinary Tract Infection Pattern. 2010 Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 184:1, s. 286-291 Tidskriftsartikel (refereegranskat)abstract PURPOSE: We evaluated the difference in the febrile urinary tract infection rate in small children with dilating vesicoureteral reflux randomly allocated to 3 management alternatives, including antibiotic prophylaxis, endoscopic treatment or surveillance only as the control. MATERIALS AND METHODS: At 23 centers a total of 203 children were included in the study, including 128 girls and 75 boys 1 to younger than 2 years. Vesicoureteral reflux grade III in 126 cases and IV in 77 was detected after a febrile urinary tract infection (194) after prenatal screening (9). Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before randomization and after 2 years. The febrile urinary tract infection rate was analyzed by the intent to treat principle. RESULTS: We noted a total of 67 febrile recurrences in 42 girls and a total of 8 in 7 boys (p = 0.0001). There was a difference in the recurrence rate among treatment groups in girls with febrile infection in 8 of 43 (19%) on prophylaxis, 10 of 43 (23%) with endoscopic therapy and 24 of 42 (57%) on surveillance (p = 0.0002). In girls the recurrence rate was associated with persistent reflux after 2 years (p = 0.0095). However, reflux severity (grade III or IV) at study entry did not predict recurrence. CONCLUSIONS: In this randomized, controlled trial there was a high rate of recurrent febrile urinary tract infection in girls older than 1 year with dilating vesicoureteral reflux at study entry but not in boys. Antibiotic prophylaxis and endoscopic treatment decreased the infection rate.

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